Standing on the shoulders of giants: How a Novavax vaccine is developed

Learning from a century of vaccine development

Vaccines have been used for hundreds of years to change people’s lives for the better by helping to prevent certain diseases and associated deaths. And that is not their only benefit. Vaccines also help reduce the burden on healthcare systems, provide major economic benefits, and reduce costs to society.1,2 In fact, only access to clean water has had a greater positive impact on global health than vaccines.2

Over the last 50 years, improvements in knowledge and understanding of the immune system and genetic engineering have provided the stimulus to develop vaccination programs that have almost eliminated many infectious pathogens like those causing measles and rubella3; these now save about 4 to 5 million lives per year.4

At Novavax, we use a combination of historic understanding, advanced research technologies, and powerful, new techniques to produce protein-based vaccine candidates. This type of vaccine uses a single protein component (antigen) from the pathogen (eg, a bacteria or virus) to stimulate an immune response and train the body to recognize the whole pathogen.5,6

This established technique has been used successfully for decades to immunize against infectious diseases, such as diphtheria and tetanus.6,7 Using only the essential antigens in a vaccine, rather than an entire attenuated (weakened) version of the pathogen, can make vaccines easier to produce and may reduce their side effects.6

The introduction of genetic engineering at the end of the 20th century enabled scientists to edit and combine DNA/RNA from multiple sources to create recombinant genes and proteins. By using this approach, researchers can edit antigens and make them more suitable to be included in a vaccine, for example, by making them more stable.3,8 Recombinant protein-based vaccines have been used for years to target infectious diseases such as hepatitis B and human papillomavirus (HPV).5,6

Potential ingredients found in a vaccine9

Part of the pathogen that generates an immune response


A substance added to the vaccine to enhance the immune response

Preservatives, stabilizers, surfactants

Prevent contamination, prevent chemical reactions, and keep the ingredients blended together

Vaccine development at Novavax

Our vaccines are based on tried-and-tested techniques and employ the use of technology—each of our recombinant proteins are attached to a nanoparticle core and mixed with our proprietary Matrix-M™ adjuvant.

Nanoparticle core
Our recombinant proteins form a structure around a central nanoparticle, which is a tiny structure, often no larger than the virus itself. In this way, the immune system can learn to recognize the antigen from multiple angles, possibly improving the ability to identify and help neutralize a pathogen.

Matrix-M™ adjuvant
Matrix-M™ is a soccer-ball shaped particle that we mixed with our recombinant, protein-based nanoparticles to stimulate the immune system, which may improve the immune response to our vaccines.10–12

Antigen is part of the pathogen that generates immune response.

Not to scale. Matrixtm adjuvant is larger than the vaccine nanoparticle.

Not to scale. Matrix-M™ adjuvant is larger than the vaccine nanoparticle.

To make our vaccines, we mix this recombinant, protein-based nanoparticle with our proprietary Matrix-M adjuvant, which helps to stimulate the immune system and possibly enhance the immune response of our vaccines.11,12

6 steps to producing a Novavax investigational vaccine:

  1. After identifying an antigen that can be used to stimulate an immune response against the virus in question, the corresponding gene is modified and inserted into a baculovirus (a type of insect virus).
  2. The baculovirus containing the recombinant antigen gene is used to infect cells from a certain type of moth (called Sf9 cells); the baculovirus multiplies (replicates) inside these cells.
  3. As part of this replication process, the recombinant antigen gene from the baculovirus enters the Sf9 cell nucleus where it is transcribed into mRNA.
  4. The natural machinery in the Sf9 cells translates the mRNA to produce large quantities of the recombinant antigen protein.
  5. The recombinant antigen proteins are harvested from the surface of the Sf9 cells, purified, and arranged around a nanoparticle core.
  6. The recombinant antigen protein nanoparticles are mixed with the Matrix-M adjuvant to create the investigational vaccine.

Why we use living cells

We use living cells to produce the antigen, rather than a synthetic equivalent, because the living cells contain all of the natural components needed to efficiently create a protein in its native state—ie, a protein that is correctly folded and edited. To recreate this in a cell-free system, eg, using machines, is very complicated, and although advances have been made, the process remains challenging.13

When the antigen is harvested from the moth cells (Sf9), it is extensively purified and refined.

Since our vaccine is a manufactured subunit of the virus, it does not use any infectious part of the virus and only recombinant proteins to stimulate an immune response. Our vaccines cannot cause the disease they are attempting to help protect against. Instead they imitate an infectious particle so that the immune system can learn to respond to the antigen.14

After a vaccine has been developed

As with all medicines, every vaccine must go through a series of extensive and robust clinical trials before being approved for use.9

  • Preclinical phase: The vaccine is tested in cells in a laboratory and in animal models to make sure it stimulates an immune response9
  • Phase 1: The vaccine is tested in a small number of healthy volunteers to make sure it is safe for use in humans and that it stimulates an immune response. Different doses and formulations of the vaccine may be tested9
  • Phase 2: The vaccine is tested in several hundred volunteers to further assess its safety and efficacy. Different doses and formulations may be tested and are usually compared with a placebo9
  • Phase 3: Thousands of volunteers receive the vaccine or a placebo to compare how effective it is in generating an immune response and to study its safety in a much larger group9

In many phase 2 and 3 clinical trials, neither the participants, the scientists, nor the doctors involved in the study know who is getting the vaccine being tested and who is getting the comparator (or placebo) product, so no one can knowingly influence the results. This is known as “blinding.”9

Once the clinical studies have been completed, the data are analyzed by regulatory authorities to decide whether the vaccine is safe and effective to be approved for use. Once a vaccine has been approved, information on side effects continues to be collected to monitor its safety over time.9 Vaccine effectiveness is also monitored after approval.

For more information on clinical trials, visit our safety and efficacy page.

  1. Largeron N, et al. J Mark Access Health Policy. 2015;3:10.
  2. Andre FE, et al. Bull World Health Organ. 2008;86(2):140–146.
  3. McCullers JA, Dunn JD. P&T. 2008;33:35–41.
  4. Immunization. World Health Organization (WHO). Available at: [Accessed 27 Aug 2021].
  5. How vaccines work. Public Health. Available at: [Accessed 27 Aug 2021].
  6. Vaccine types. National Institute of Allergy and Infectious Diseases. Available at: [Accessed 27 Aug 2021].
  7. Plotkin S. Proc Natl Acad Sci U S A. 2014;111(34):12283–12287.
  8. Agadjanyan MG, et al. Alzheimers Dement. 2015;11(10):1246–1259.
  9. How are vaccines developed. WHO. Available at: [Accessed 27 Aug 2021].
  10. Pulendran B, et al. Nat Rev Drug Discov. 2021;20(6):454–475.
  11. Keech C, et al. N Engl J Med. 2020;383(24):2320–2332.
  12. Fries L, et al. J Infect Dis. 2020;222(4):572–582.
  13. Legastelois I, et al. Hum Vaccin Immunother. 2016;13(4):947–961.
  14. Understanding how vaccines work. Centers for Disease Control and Prevention. Available at: [Accessed 27 Aug 2021].
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